Study on Difference of Genotypes of Patients with Coronary Artery Disease and Different Responses to Clopidogrel
10.6039/j.issn.1001-0408.2017.11.03
- VernacularTitle:对氯吡格雷不同反应的冠状动脉疾病患者基因型差异研究
- Author:
Anning ZENG
;
Degao XIONG
;
Jian SHI
;
Jixi YU
;
Rongxing CHEN
;
Bingbing CAI
- Keywords:
CYP2C19;
CYP3A5;
PLA1/PLA2;
Gene polymorphisms;
Clopidogrel;
Resistance
- From:
China Pharmacy
2017;28(11):1448-1452
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the difference of genotypes in patients with coronary artery disease(CAD)and different responses to clopidogrel. METHODS:Totally 159 CAD patients were selected from cardiology department of our hospital during Mar. 2013-Nov. 2015. They were given clopidogrel+aspirin for dual antiplatelet therapy for at least 1 year. Turbidimetry method was used to detect the percentage of platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid (AA) before and after treatment. The polymorphism of cytochrome P450(CYP)2C19,CYP3A5,wild type leucine 33 allele(PLA1)/proline 33 al-lele(PLA2)were detected by PCR-RFLP. RESULTS:There were 3 kinds of CYP2C19 genotypes(2/2,2/1,1/1),3 kinds of CYP3A5 genotypes (3/3,3/1,1/1) and 3 kinds of PLA1/PLA2 genotypes (A1/A2,A2/A2,A1/A1);the frequency of each genotype was in line with Hardy-Weinberg balance(P>0.05). Among 159 cases,there were 81 cases of clopidogrelsemi-re-sponse,accounting for 50.9%;78 cases of clopidogrelresponse,accounting for 49.1%. The frequencies of CYP2C19 gene dele-tion(2/2 or 2/1 genotype)and 2 allele in clopidogrelsemi-responsepatients were significantly higher than clopidogrelre-sponsepatients,with statistical significance(P<0.05). The frequencies of PLA1/PLA2 gene deletion(A2/A2 or A1/A2 genotype) and A2 allele in clopidogrelsemi-responsepatients were significantly higher than clopidogrelresponsepatients,with statistical significance(P<0.05). The frequencies of CYP3A5 gene deletion(3/3 or 3/1 genotype)and 3 allele in clopidogrelsemi-re-sponsepatients were slightly higher than clopidogrelresponsepatients,without statistical significance (P>0.05). After treat-ment,the percentage of ADP or AA-induced platelet aggregation in different genotypes patients were significantly lowered,com-pared to before treatment;but the percentage of platelet aggregation in CYP2C19 gene deletion and CYP3A5 gene deletion patients were significantly higher than gene expression patients(1/1 genotype),with statistical significance(P<0.05). There was no sta-tistical significance in the percentage of platelet aggregation between PLA1/PLA2 gene deletion patients and gene expression patients (P>0.05). CONCLUSIONS:The incidence of clopidogrelsemi-responsein CAD patients is high. CYP2C19 and PLA1/PLA2 gene polymorphism may be related to clopidogrelsemi-re-sponse,while CYP3A5 gene polymorphism has no relation-ship with it. CYP2C19 and CYP3A5 gene deletion may weaken inhibitory effects of clopidogrel on platelet aggregation of CAD patients.
